CN85101547A - 新型八氢噻唑[4，5-g]并喹啉化合物的制备方法及其用途 - Google Patents

新型八氢噻唑[4，5-g]并喹啉化合物的制备方法及其用途 Download PDF

Info

Publication number: CN85101547A
Authority: CN; China
Prior art keywords: propyl; quinoline; compound; thiazole; octahydro
Prior art date: 1984-04-27
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.): Pending

Application number

CN198585101547A

Other languages

English (en)

Chinese (zh)

Inventor

罗伯特·丹尼尔·泰特斯

埃德蒙·卡尔·科恩菲尔德

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

Eli Lilly and Co

Original Assignee

Eli Lilly and Co

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

1984-04-27

Filing date

1985-04-01

Publication date

1987-01-24

1985-04-01 Application filed by Eli Lilly and Co filed Critical Eli Lilly and Co

1985-04-01 Priority to CN198585101547A priority Critical patent/CN85101547A/zh

1987-01-24 Publication of CN85101547A publication Critical patent/CN85101547A/zh

Status Pending legal-status Critical Current

Links

SMWDFEZZVXVKRB-UHFFFAOYSA-N anhydrous quinoline Natural products N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 title claims abstract description 137
FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 title claims abstract description 73
-1 quinoline compound Chemical class 0.000 title claims description 29
238000002360 preparation method Methods 0.000 title claims description 25
150000003839 salts Chemical group 0.000 claims abstract description 43
239000002253 acid Substances 0.000 claims abstract description 34
150000001875 compounds Chemical class 0.000 claims description 101
238000000034 method Methods 0.000 claims description 41
239000001257 hydrogen Substances 0.000 claims description 36
229910052739 hydrogen Inorganic materials 0.000 claims description 36
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 30
238000006243 chemical reaction Methods 0.000 claims description 27
125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 25
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 23
UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 claims description 23
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 22
239000007864 aqueous solution Substances 0.000 claims description 20
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 18
CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 claims description 17
125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 16
229910052794 bromium Inorganic materials 0.000 claims description 15
125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 11
230000004048 modification Effects 0.000 claims description 11
238000012986 modification Methods 0.000 claims description 11
239000000376 reactant Substances 0.000 claims description 10
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 9
229910052801 chlorine Inorganic materials 0.000 claims description 8
238000005917 acylation reaction Methods 0.000 claims description 6
229910052736 halogen Inorganic materials 0.000 claims description 5
150000002367 halogens Chemical class 0.000 claims description 5
RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 4
150000001350 alkyl halides Chemical class 0.000 claims description 4
239000012954 diazonium Substances 0.000 claims description 4
KQJQICVXLJTWQD-UHFFFAOYSA-N N-Methylthiourea Chemical compound CNC(N)=S KQJQICVXLJTWQD-UHFFFAOYSA-N 0.000 claims description 3
WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 claims description 3
239000012346 acetyl chloride Substances 0.000 claims description 3
150000001989 diazonium salts Chemical class 0.000 claims description 3
150000002500 ions Chemical class 0.000 claims description 3
229910017604 nitric acid Inorganic materials 0.000 claims description 3
238000007363 ring formation reaction Methods 0.000 claims description 3
RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 claims description 2
JPVYNHNXODAKFH-UHFFFAOYSA-N Cu2+ Chemical compound [Cu+2] JPVYNHNXODAKFH-UHFFFAOYSA-N 0.000 claims description 2
XGEGHDBEHXKFPX-UHFFFAOYSA-N N-methylthiourea Natural products CNC(N)=O XGEGHDBEHXKFPX-UHFFFAOYSA-N 0.000 claims description 2
125000005843 halogen group Chemical group 0.000 claims description 2
CYEBJEDOHLIWNP-UHFFFAOYSA-N methanethioamide Chemical compound NC=S CYEBJEDOHLIWNP-UHFFFAOYSA-N 0.000 claims 2
229910001431 copper ion Inorganic materials 0.000 claims 1
CTENFNNZBMHDDG-UHFFFAOYSA-N Dopamine hydrochloride Chemical compound Cl.NCCC1=CC=C(O)C(O)=C1 CTENFNNZBMHDDG-UHFFFAOYSA-N 0.000 abstract description 16
238000013507 mapping Methods 0.000 abstract 1
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 83
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 62
235000002639 sodium chloride Nutrition 0.000 description 42
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 38
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 35
239000000243 solution Substances 0.000 description 30
239000003513 alkali Substances 0.000 description 26
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 24
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 24
239000003814 drug Substances 0.000 description 20
239000011541 reaction mixture Substances 0.000 description 17
239000007787 solid Substances 0.000 description 17
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 16
241000700159 Rattus Species 0.000 description 14
VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 14
238000000605 extraction Methods 0.000 description 14
239000000203 mixture Substances 0.000 description 14
239000000460 chlorine Substances 0.000 description 13
230000000694 effects Effects 0.000 description 13
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 12
102000003946 Prolactin Human genes 0.000 description 12
108010057464 Prolactin Proteins 0.000 description 12
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
229940097325 prolactin Drugs 0.000 description 12
229960000583 acetic acid Drugs 0.000 description 11
239000007788 liquid Substances 0.000 description 11
238000001953 recrystallisation Methods 0.000 description 11
229960004756 ethanol Drugs 0.000 description 10
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 10
239000000047 product Substances 0.000 description 10
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 9
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 9
125000000217 alkyl group Chemical group 0.000 description 9
239000013078 crystal Substances 0.000 description 9
239000003480 eluent Substances 0.000 description 9
239000007789 gas Substances 0.000 description 9
239000012362 glacial acetic acid Substances 0.000 description 9
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 9
229910000041 hydrogen chloride Inorganic materials 0.000 description 9
239000002904 solvent Substances 0.000 description 9
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 8
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 8
229910000042 hydrogen bromide Inorganic materials 0.000 description 8
150000002576 ketones Chemical class 0.000 description 8
FKHIFSZMMVMEQY-UHFFFAOYSA-N talc Chemical compound [Mg+2].[O-][Si]([O-])=O FKHIFSZMMVMEQY-UHFFFAOYSA-N 0.000 description 8
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 7
229960003638 dopamine Drugs 0.000 description 7
229920006395 saturated elastomer Polymers 0.000 description 7
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 7
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 6
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
206010020772 Hypertension Diseases 0.000 description 6
239000004480 active ingredient Substances 0.000 description 6
239000002585 base Substances 0.000 description 6
238000004587 chromatography analysis Methods 0.000 description 6
239000012065 filter cake Substances 0.000 description 6
238000001914 filtration Methods 0.000 description 6
VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 6
238000001819 mass spectrum Methods 0.000 description 6
BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 6
238000002156 mixing Methods 0.000 description 6
NYWQXKOAQGNXBO-UHFFFAOYSA-N quinoline;dihydrobromide Chemical compound Br.Br.N1=CC=CC2=CC=CC=C21 NYWQXKOAQGNXBO-UHFFFAOYSA-N 0.000 description 6
238000010992 reflux Methods 0.000 description 6
238000001228 spectrum Methods 0.000 description 6
238000004809 thin layer chromatography Methods 0.000 description 6
229920002472 Starch Polymers 0.000 description 5
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 5
238000005893 bromination reaction Methods 0.000 description 5
239000002775 capsule Substances 0.000 description 5
238000001816 cooling Methods 0.000 description 5
229960000935 dehydrated alcohol Drugs 0.000 description 5
201000010099 disease Diseases 0.000 description 5
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 5
238000002474 experimental method Methods 0.000 description 5
238000010438 heat treatment Methods 0.000 description 5
XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 5
235000019359 magnesium stearate Nutrition 0.000 description 5
238000006722 reduction reaction Methods 0.000 description 5
230000028327 secretion Effects 0.000 description 5
239000008107 starch Substances 0.000 description 5
229940032147 starch Drugs 0.000 description 5
235000019698 starch Nutrition 0.000 description 5
229940095064 tartrate Drugs 0.000 description 5
208000018737 Parkinson disease Diseases 0.000 description 4
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
229910000147 aluminium phosphate Inorganic materials 0.000 description 4
230000001430 anti-depressive effect Effects 0.000 description 4
239000000935 antidepressant agent Substances 0.000 description 4
229910052799 carbon Inorganic materials 0.000 description 4
230000008859 change Effects 0.000 description 4
239000003795 chemical substances by application Substances 0.000 description 4
238000001035 drying Methods 0.000 description 4
230000005764 inhibitory process Effects 0.000 description 4
238000002347 injection Methods 0.000 description 4
239000007924 injection Substances 0.000 description 4
239000000543 intermediate Substances 0.000 description 4
238000001556 precipitation Methods 0.000 description 4
LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 4
IRFHMTUHTBSEBK-QGZVFWFLSA-N tert-butyl n-[(2s)-2-(2,5-difluorophenyl)-3-quinolin-3-ylpropyl]carbamate Chemical compound C1([C@H](CC=2C=C3C=CC=CC3=NC=2)CNC(=O)OC(C)(C)C)=CC(F)=CC=C1F IRFHMTUHTBSEBK-QGZVFWFLSA-N 0.000 description 4
238000005406 washing Methods 0.000 description 4
OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 3
DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 3
208000019901 Anxiety disease Diseases 0.000 description 3
229920000168 Microcrystalline cellulose Polymers 0.000 description 3
239000000370 acceptor Substances 0.000 description 3
DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 description 3
239000000908 ammonium hydroxide Substances 0.000 description 3
125000003118 aryl group Chemical group 0.000 description 3
230000006399 behavior Effects 0.000 description 3
238000004364 calculation method Methods 0.000 description 3
239000007795 chemical reaction product Substances 0.000 description 3
238000002425 crystallisation Methods 0.000 description 3
229940079593 drug Drugs 0.000 description 3
230000004064 dysfunction Effects 0.000 description 3
235000019253 formic acid Nutrition 0.000 description 3
PSXRWZBTVAZNSF-UHFFFAOYSA-N hydron;quinoline;chloride Chemical compound Cl.N1=CC=CC2=CC=CC=C21 PSXRWZBTVAZNSF-UHFFFAOYSA-N 0.000 description 3
230000001631 hypertensive effect Effects 0.000 description 3
INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 3
229940016286 microcrystalline cellulose Drugs 0.000 description 3
235000019813 microcrystalline cellulose Nutrition 0.000 description 3
239000008108 microcrystalline cellulose Substances 0.000 description 3
239000011259 mixed solution Substances 0.000 description 3
239000012046 mixed solvent Substances 0.000 description 3
230000008092 positive effect Effects 0.000 description 3
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Substances [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 3
235000015320 potassium carbonate Nutrition 0.000 description 3
BTUQCUPQFZHMNS-UHFFFAOYSA-N quinoline;dihydrochloride Chemical compound Cl.Cl.N1=CC=CC2=CC=CC=C21 BTUQCUPQFZHMNS-UHFFFAOYSA-N 0.000 description 3
238000000926 separation method Methods 0.000 description 3
230000009329 sexual behaviour Effects 0.000 description 3
238000003756 stirring Methods 0.000 description 3
239000000725 suspension Substances 0.000 description 3
150000003557 thiazoles Chemical class 0.000 description 3
238000009281 ultraviolet germicidal irradiation Methods 0.000 description 3
SFLSHLFXELFNJZ-QMMMGPOBSA-N (-)-norepinephrine Chemical compound NC[C@H](O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-QMMMGPOBSA-N 0.000 description 2
INOPOHSUVXSUKY-BTJKTKAUSA-N (z)-but-2-enedioic acid;quinoline Chemical compound OC(=O)\C=C/C(O)=O.N1=CC=CC2=CC=CC=C21 INOPOHSUVXSUKY-BTJKTKAUSA-N 0.000 description 2
CEKSPMMCISUSTR-UHFFFAOYSA-N 1,2,3,4,4a,5,6,7-octahydroquinoline Chemical compound C1CCC2CCCNC2=C1 CEKSPMMCISUSTR-UHFFFAOYSA-N 0.000 description 2
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 2
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
239000005711 Benzoic acid Substances 0.000 description 2
LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 2
206010017600 Galactorrhoea Diseases 0.000 description 2
239000001828 Gelatine Substances 0.000 description 2
AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 2
241000124008 Mammalia Species 0.000 description 2
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 2
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
238000010306 acid treatment Methods 0.000 description 2
WYTGDNHDOZPMIW-RCBQFDQVSA-N alstonine Natural products C1=CC2=C3C=CC=CC3=NC2=C2N1C[C@H]1[C@H](C)OC=C(C(=O)OC)[C@H]1C2 WYTGDNHDOZPMIW-RCBQFDQVSA-N 0.000 description 2
238000004458 analytical method Methods 0.000 description 2
235000010233 benzoic acid Nutrition 0.000 description 2
230000036772 blood pressure Effects 0.000 description 2
230000037396 body weight Effects 0.000 description 2
210000004556 brain Anatomy 0.000 description 2
230000031709 bromination Effects 0.000 description 2
125000004432 carbon atom Chemical group C* 0.000 description 2
239000001913 cellulose Substances 0.000 description 2
235000010980 cellulose Nutrition 0.000 description 2
229920002678 cellulose Polymers 0.000 description 2
238000013375 chromatographic separation Methods 0.000 description 2
239000000470 constituent Substances 0.000 description 2
230000008025 crystallization Effects 0.000 description 2
238000006193 diazotization reaction Methods 0.000 description 2
238000004090 dissolution Methods 0.000 description 2
DGXRZJSPDXZJFG-UHFFFAOYSA-N docosanedioic acid Chemical compound OC(=O)CCCCCCCCCCCCCCCCCCCCC(O)=O DGXRZJSPDXZJFG-UHFFFAOYSA-N 0.000 description 2
238000001704 evaporation Methods 0.000 description 2
230000008020 evaporation Effects 0.000 description 2
230000003203 everyday effect Effects 0.000 description 2
230000004927 fusion Effects 0.000 description 2
229920000159 gelatin Polymers 0.000 description 2
235000019322 gelatine Nutrition 0.000 description 2
230000007062 hydrolysis Effects 0.000 description 2
238000006460 hydrolysis reaction Methods 0.000 description 2
239000003112 inhibitor Substances 0.000 description 2
229910052500 inorganic mineral Inorganic materials 0.000 description 2
VNWKTOKETHGBQD-UHFFFAOYSA-N methane Natural products C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 2
235000010755 mineral Nutrition 0.000 description 2
239000011707 mineral Substances 0.000 description 2
150000004712 monophosphates Chemical class 0.000 description 2
229910052757 nitrogen Inorganic materials 0.000 description 2
231100000956 nontoxicity Toxicity 0.000 description 2
229960002748 norepinephrine Drugs 0.000 description 2
SFLSHLFXELFNJZ-UHFFFAOYSA-N norepinephrine Natural products NCC(O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-UHFFFAOYSA-N 0.000 description 2
150000007524 organic acids Chemical class 0.000 description 2
239000008188 pellet Substances 0.000 description 2
239000012071 phase Substances 0.000 description 2
150000003016 phosphoric acids Chemical class 0.000 description 2
239000000049 pigment Substances 0.000 description 2
229920000036 polyvinylpyrrolidone Polymers 0.000 description 2
235000013855 polyvinylpyrrolidone Nutrition 0.000 description 2
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
230000008569 process Effects 0.000 description 2
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
238000000746 purification Methods 0.000 description 2
239000002994 raw material Substances 0.000 description 2
230000001568 sexual effect Effects 0.000 description 2
229910000033 sodium borohydride Inorganic materials 0.000 description 2
239000012279 sodium borohydride Substances 0.000 description 2
JHJLBTNAGRQEKS-UHFFFAOYSA-M sodium bromide Chemical compound [Na+].[Br-] JHJLBTNAGRQEKS-UHFFFAOYSA-M 0.000 description 2
239000011780 sodium chloride Substances 0.000 description 2
229960002668 sodium chloride Drugs 0.000 description 2
235000010288 sodium nitrite Nutrition 0.000 description 2
239000008109 sodium starch glycolate Substances 0.000 description 2
229940079832 sodium starch glycolate Drugs 0.000 description 2
229920003109 sodium starch glycolate Polymers 0.000 description 2
235000014347 soups Nutrition 0.000 description 2
238000010025 steaming Methods 0.000 description 2
208000011580 syndromic disease Diseases 0.000 description 2
239000006188 syrup Substances 0.000 description 2
235000020357 syrup Nutrition 0.000 description 2
239000000454 talc Substances 0.000 description 2
235000012222 talc Nutrition 0.000 description 2
229910052623 talc Inorganic materials 0.000 description 2
238000012360 testing method Methods 0.000 description 2
230000001225 therapeutic effect Effects 0.000 description 2
YUKQRDCYNOVPGJ-UHFFFAOYSA-N thioacetamide Chemical compound CC(N)=S YUKQRDCYNOVPGJ-UHFFFAOYSA-N 0.000 description 2
WDCYWAQPCXBPJA-UHFFFAOYSA-N 1,3-dinitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC([N+]([O-])=O)=C1 WDCYWAQPCXBPJA-UHFFFAOYSA-N 0.000 description 1
WURBVZBTWMNKQT-UHFFFAOYSA-N 1-(4-chlorophenoxy)-3,3-dimethyl-1-(1,2,4-triazol-1-yl)butan-2-one Chemical compound C1=NC=NN1C(C(=O)C(C)(C)C)OC1=CC=C(Cl)C=C1 WURBVZBTWMNKQT-UHFFFAOYSA-N 0.000 description 1
PNYRDWUKTXFTPN-UHFFFAOYSA-M 1-methylquinolin-1-ium;iodide Chemical compound [I-].C1=CC=C2[N+](C)=CC=CC2=C1 PNYRDWUKTXFTPN-UHFFFAOYSA-M 0.000 description 1
QFTAAIXFZNESMI-UHFFFAOYSA-N 2,3,4,4a,5,7,8,8a-octahydro-1h-quinolin-6-one Chemical compound N1CCCC2CC(=O)CCC21 QFTAAIXFZNESMI-UHFFFAOYSA-N 0.000 description 1
OPBYRXVXJSNMKM-UHFFFAOYSA-N 2,3-dihydroxybutanedioic acid;quinoline Chemical compound N1=CC=CC2=CC=CC=C21.OC(=O)C(O)C(O)C(O)=O OPBYRXVXJSNMKM-UHFFFAOYSA-N 0.000 description 1
125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 1
BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
WHBMMWSBFZVSSR-UHFFFAOYSA-N 3-hydroxybutyric acid Chemical class CC(O)CC(O)=O WHBMMWSBFZVSSR-UHFFFAOYSA-N 0.000 description 1
QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 1
OBKXEAXTFZPCHS-UHFFFAOYSA-N 4-phenylbutyric acid Chemical class OC(=O)CCCC1=CC=CC=C1 OBKXEAXTFZPCHS-UHFFFAOYSA-N 0.000 description 1
AWFDCTXCTHGORH-HGHGUNKESA-N 6-[4-[(6ar,9r,10ar)-5-bromo-7-methyl-6,6a,8,9,10,10a-hexahydro-4h-indolo[4,3-fg]quinoline-9-carbonyl]piperazin-1-yl]-1-methylpyridin-2-one Chemical group O=C([C@H]1CN([C@H]2[C@@H](C=3C=CC=C4NC(Br)=C(C=34)C2)C1)C)N(CC1)CCN1C1=CC=CC(=O)N1C AWFDCTXCTHGORH-HGHGUNKESA-N 0.000 description 1
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 1
NIXOWILDQLNWCW-UHFFFAOYSA-M Acrylate Chemical compound [O-]C(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-M 0.000 description 1
238000006027 Birch reduction reaction Methods 0.000 description 1
CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
GBDVIAUJHSJJNF-UHFFFAOYSA-N C(C1=CC=C(C(=O)O)C=C1)(=O)O.N1=CC=CC2=CC=CC=C12 Chemical compound C(C1=CC=C(C(=O)O)C=C1)(=O)O.N1=CC=CC2=CC=CC=C12 GBDVIAUJHSJJNF-UHFFFAOYSA-N 0.000 description 1
JGLMVXWAHNTPRF-CMDGGOBGSA-N CCN1N=C(C)C=C1C(=O)NC1=NC2=CC(=CC(OC)=C2N1C\C=C\CN1C(NC(=O)C2=CC(C)=NN2CC)=NC2=CC(=CC(OCCCN3CCOCC3)=C12)C(N)=O)C(N)=O Chemical compound CCN1N=C(C)C=C1C(=O)NC1=NC2=CC(=CC(OC)=C2N1C\C=C\CN1C(NC(=O)C2=CC(C)=NN2CC)=NC2=CC(=CC(OCCCN3CCOCC3)=C12)C(N)=O)C(N)=O JGLMVXWAHNTPRF-CMDGGOBGSA-N 0.000 description 1
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
101150049660 DRD2 gene Proteins 0.000 description 1
FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 description 1
229940098778 Dopamine receptor agonist Drugs 0.000 description 1
241000196324 Embryophyta Species 0.000 description 1
DNXHEGUUPJUMQT-CBZIJGRNSA-N Estrone Chemical compound OC1=CC=C2[C@H]3CC[C@](C)(C(CC4)=O)[C@@H]4[C@@H]3CCC2=C1 DNXHEGUUPJUMQT-CBZIJGRNSA-N 0.000 description 1
BDAGIHXWWSANSR-UHFFFAOYSA-M Formate Chemical compound [O-]C=O BDAGIHXWWSANSR-UHFFFAOYSA-M 0.000 description 1
VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 1
208000001287 Galactorrhea Diseases 0.000 description 1
244000287680 Garcinia dulcis Species 0.000 description 1
208000001953 Hypotension Diseases 0.000 description 1
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 1
208000019395 Lactation disease Diseases 0.000 description 1
OFOBLEOULBTSOW-UHFFFAOYSA-L Malonate Chemical compound [O-]C(=O)CC([O-])=O OFOBLEOULBTSOW-UHFFFAOYSA-L 0.000 description 1
241001465754 Metazoa Species 0.000 description 1
101000869659 Mus musculus Relaxin receptor 2 Proteins 0.000 description 1
WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 1
229910002651 NO3 Inorganic materials 0.000 description 1
NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 1
229910019142 PO4 Inorganic materials 0.000 description 1
206010033799 Paralysis Diseases 0.000 description 1
OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
235000021355 Stearic acid Nutrition 0.000 description 1
ZZXDRXVIRVJQBT-UHFFFAOYSA-M Xylenesulfonate Chemical compound CC1=CC=CC(S([O-])(=O)=O)=C1C ZZXDRXVIRVJQBT-UHFFFAOYSA-M 0.000 description 1
XVDSAUWKVZOUMO-UHFFFAOYSA-N [N+](=O)([O-])C=1C(=C(C(=O)O)C=CC1)[N+](=O)[O-].N1=CC=CC2=CC=CC=C12 Chemical compound [N+](=O)([O-])C=1C(=C(C(=O)O)C=CC1)[N+](=O)[O-].N1=CC=CC2=CC=CC=C12 XVDSAUWKVZOUMO-UHFFFAOYSA-N 0.000 description 1
ZYBXCIBWFOILPE-UHFFFAOYSA-N [Na].N#CC#N Chemical compound [Na].N#CC#N ZYBXCIBWFOILPE-UHFFFAOYSA-N 0.000 description 1
GTECZFVZNHCHKM-UHFFFAOYSA-N [P].N1=CC=CC2=CC=CC=C21 Chemical compound [P].N1=CC=CC2=CC=CC=C21 GTECZFVZNHCHKM-UHFFFAOYSA-N 0.000 description 1
230000002159 abnormal effect Effects 0.000 description 1
IPBVNPXQWQGGJP-UHFFFAOYSA-N acetic acid phenyl ester Natural products CC(=O)OC1=CC=CC=C1 IPBVNPXQWQGGJP-UHFFFAOYSA-N 0.000 description 1
230000002378 acidificating effect Effects 0.000 description 1
150000007513 acids Chemical class 0.000 description 1
238000004378 air conditioning Methods 0.000 description 1
125000001931 aliphatic group Chemical group 0.000 description 1
BHELZAPQIKSEDF-UHFFFAOYSA-N allyl bromide Chemical compound BrCC=C BHELZAPQIKSEDF-UHFFFAOYSA-N 0.000 description 1
238000005937 allylation reaction Methods 0.000 description 1
125000000746 allylic group Chemical group 0.000 description 1
PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 1
150000001408 amides Chemical class 0.000 description 1
229910021529 ammonia Inorganic materials 0.000 description 1
238000010171 animal model Methods 0.000 description 1
239000005557 antagonist Substances 0.000 description 1
230000003276 anti-hypertensive effect Effects 0.000 description 1
239000002249 anxiolytic agent Substances 0.000 description 1
238000013459 approach Methods 0.000 description 1
239000008346 aqueous phase Substances 0.000 description 1
239000007900 aqueous suspension Substances 0.000 description 1
150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
239000003637 basic solution Substances 0.000 description 1
229940077388 benzenesulfonate Drugs 0.000 description 1
SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 description 1
230000015572 biosynthetic process Effects 0.000 description 1
210000004204 blood vessel Anatomy 0.000 description 1
238000009835 boiling Methods 0.000 description 1
125000001246 bromo group Chemical class Br* 0.000 description 1
CNULTVPLQNIZNP-UHFFFAOYSA-N butanedioic acid;quinoline Chemical compound OC(=O)CCC(O)=O.N1=CC=CC2=CC=CC=C21 CNULTVPLQNIZNP-UHFFFAOYSA-N 0.000 description 1
235000012970 cakes Nutrition 0.000 description 1
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
XTEGARKTQYYJKE-UHFFFAOYSA-N chloric acid Chemical compound OCl(=O)=O XTEGARKTQYYJKE-UHFFFAOYSA-N 0.000 description 1
KVSASDOGYIBWTA-UHFFFAOYSA-N chloro benzoate Chemical compound ClOC(=O)C1=CC=CC=C1 KVSASDOGYIBWTA-UHFFFAOYSA-N 0.000 description 1
238000011097 chromatography purification Methods 0.000 description 1
229950002314 closilate Drugs 0.000 description 1
239000012141 concentrate Substances 0.000 description 1
235000008504 concentrate Nutrition 0.000 description 1
JZCCFEFSEZPSOG-UHFFFAOYSA-L copper(II) sulfate pentahydrate Chemical compound O.O.O.O.O.[Cu+2].[O-]S([O-])(=O)=O JZCCFEFSEZPSOG-UHFFFAOYSA-L 0.000 description 1
GHVNFZFCNZKVNT-UHFFFAOYSA-M decanoate Chemical compound CCCCCCCCCC([O-])=O GHVNFZFCNZKVNT-UHFFFAOYSA-M 0.000 description 1
238000000354 decomposition reaction Methods 0.000 description 1
XPPKVPWEQAFLFU-UHFFFAOYSA-J diphosphate(4-) Chemical class [O-]P([O-])(=O)OP([O-])([O-])=O XPPKVPWEQAFLFU-UHFFFAOYSA-J 0.000 description 1
238000004821 distillation Methods 0.000 description 1
GRWZHXKQBITJKP-UHFFFAOYSA-N dithionous acid Chemical compound OS(=O)S(O)=O GRWZHXKQBITJKP-UHFFFAOYSA-N 0.000 description 1
239000003136 dopamine receptor stimulating agent Substances 0.000 description 1
235000021463 dry cake Nutrition 0.000 description 1
125000002587 enol group Chemical class 0.000 description 1
RHGUXDUPXYFCTE-ZWNOBZJWSA-N ergoline Chemical class C1=CC([C@@H]2[C@H](NCCC2)C2)=C3C2=CNC3=C1 RHGUXDUPXYFCTE-ZWNOBZJWSA-N 0.000 description 1
238000011156 evaluation Methods 0.000 description 1
239000000706 filtrate Substances 0.000 description 1
239000012467 final product Substances 0.000 description 1
235000013305 food Nutrition 0.000 description 1
230000026030 halogenation Effects 0.000 description 1
238000005658 halogenation reaction Methods 0.000 description 1
MNWFXJYAOYHMED-UHFFFAOYSA-M heptanoate Chemical compound CCCCCCC([O-])=O MNWFXJYAOYHMED-UHFFFAOYSA-M 0.000 description 1
150000002431 hydrogen Chemical class 0.000 description 1
WSZKUEZEYFNPID-UHFFFAOYSA-N hydrogen sulfate;quinolin-1-ium Chemical compound OS(O)(=O)=O.N1=CC=CC2=CC=CC=C21 WSZKUEZEYFNPID-UHFFFAOYSA-N 0.000 description 1
238000005984 hydrogenation reaction Methods 0.000 description 1
229940071870 hydroiodic acid Drugs 0.000 description 1
230000003301 hydrolyzing effect Effects 0.000 description 1
208000021822 hypotensive Diseases 0.000 description 1
230000001077 hypotensive effect Effects 0.000 description 1
239000005457 ice water Substances 0.000 description 1
238000010253 intravenous injection Methods 0.000 description 1
ICIWUVCWSCSTAQ-UHFFFAOYSA-M iodate Chemical compound [O-]I(=O)=O ICIWUVCWSCSTAQ-UHFFFAOYSA-M 0.000 description 1
229910052740 iodine Inorganic materials 0.000 description 1
KQNPFQTWMSNSAP-UHFFFAOYSA-N isobutyric acid Chemical compound CC(C)C(O)=O KQNPFQTWMSNSAP-UHFFFAOYSA-N 0.000 description 1
125000000468 ketone group Chemical group 0.000 description 1
210000003734 kidney Anatomy 0.000 description 1
JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical class CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 1
238000002386 leaching Methods 0.000 description 1
229940049920 malate Drugs 0.000 description 1
150000002688 maleic acid derivatives Chemical class 0.000 description 1
BJEPYKJPYRNKOW-UHFFFAOYSA-N malic acid Chemical compound OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
IWYDHOAUDWTVEP-UHFFFAOYSA-M mandelate Chemical compound [O-]C(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-M 0.000 description 1
238000004949 mass spectrometry Methods 0.000 description 1
239000002398 materia medica Substances 0.000 description 1
239000000463 material Substances 0.000 description 1
125000005341 metaphosphate group Chemical group 0.000 description 1
QDZPEBUZOMOUNJ-UHFFFAOYSA-N methanesulfonic acid;quinoline Chemical compound CS([O-])(=O)=O.[NH+]1=CC=CC2=CC=CC=C21 QDZPEBUZOMOUNJ-UHFFFAOYSA-N 0.000 description 1
150000005342 methoxybenzoic acids Chemical class 0.000 description 1
238000006011 modification reaction Methods 0.000 description 1
108700011006 mouse mighty Proteins 0.000 description 1
KVBGVZZKJNLNJU-UHFFFAOYSA-N naphthalene-2-sulfonic acid Chemical class C1=CC=CC2=CC(S(=O)(=O)O)=CC=C21 KVBGVZZKJNLNJU-UHFFFAOYSA-N 0.000 description 1
210000005036 nerve Anatomy 0.000 description 1
239000012299 nitrogen atmosphere Substances 0.000 description 1
QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
WWZKQHOCKIZLMA-UHFFFAOYSA-N octanoic acid Chemical compound CCCCCCCC(O)=O WWZKQHOCKIZLMA-UHFFFAOYSA-N 0.000 description 1
230000003647 oxidation Effects 0.000 description 1
238000007254 oxidation reaction Methods 0.000 description 1
DIVDFFZHCJEHGG-UHFFFAOYSA-N oxidopamine Chemical compound NCCC1=CC(O)=C(O)C=C1O DIVDFFZHCJEHGG-UHFFFAOYSA-N 0.000 description 1
239000001301 oxygen Substances 0.000 description 1
229910052760 oxygen Inorganic materials 0.000 description 1
229940049953 phenylacetate Drugs 0.000 description 1
WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical compound OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 description 1
239000010452 phosphate Substances 0.000 description 1
229910052698 phosphorus Inorganic materials 0.000 description 1
239000011574 phosphorus Substances 0.000 description 1
XNGIFLGASWRNHJ-UHFFFAOYSA-L phthalate(2-) Chemical compound [O-]C(=O)C1=CC=CC=C1C([O-])=O XNGIFLGASWRNHJ-UHFFFAOYSA-L 0.000 description 1
230000000704 physical effect Effects 0.000 description 1
239000003495 polar organic solvent Substances 0.000 description 1
239000001267 polyvinylpyrrolidone Substances 0.000 description 1
230000001144 postural effect Effects 0.000 description 1
229940069328 povidone Drugs 0.000 description 1
239000000843 powder Substances 0.000 description 1
239000002244 precipitate Substances 0.000 description 1
KCXFHTAICRTXLI-UHFFFAOYSA-N propane-1-sulfonic acid Chemical class CCCS(O)(=O)=O KCXFHTAICRTXLI-UHFFFAOYSA-N 0.000 description 1
UORVCLMRJXCDCP-UHFFFAOYSA-M propynoate Chemical compound [O-]C(=O)C#C UORVCLMRJXCDCP-UHFFFAOYSA-M 0.000 description 1
150000003217 pyrazoles Chemical class 0.000 description 1
YHQSXWOXIHDVHQ-UHFFFAOYSA-N quinoline;hydrobromide Chemical compound [Br-].[NH+]1=CC=CC2=CC=CC=C21 YHQSXWOXIHDVHQ-UHFFFAOYSA-N 0.000 description 1
230000009467 reduction Effects 0.000 description 1
238000011160 research Methods 0.000 description 1
230000004044 response Effects 0.000 description 1
239000011369 resultant mixture Substances 0.000 description 1
YGSDEFSMJLZEOE-UHFFFAOYSA-M salicylate Chemical compound OC1=CC=CC=C1C([O-])=O YGSDEFSMJLZEOE-UHFFFAOYSA-M 0.000 description 1
229940116351 sebacate Drugs 0.000 description 1
CXMXRPHRNRROMY-UHFFFAOYSA-L sebacate(2-) Chemical compound [O-]C(=O)CCCCCCCCC([O-])=O CXMXRPHRNRROMY-UHFFFAOYSA-L 0.000 description 1
239000013049 sediment Substances 0.000 description 1
210000002966 serum Anatomy 0.000 description 1
208000012201 sexual and gender identity disease Diseases 0.000 description 1
208000015891 sexual disease Diseases 0.000 description 1
239000000377 silicon dioxide Substances 0.000 description 1
229960001866 silicon dioxide Drugs 0.000 description 1
235000012239 silicon dioxide Nutrition 0.000 description 1
APSBXTVYXVQYAB-UHFFFAOYSA-M sodium docusate Chemical compound [Na+].CCCCC(CC)COC(=O)CC(S([O-])(=O)=O)C(=O)OCC(CC)CCCC APSBXTVYXVQYAB-UHFFFAOYSA-M 0.000 description 1
238000010183 spectrum analysis Methods 0.000 description 1
238000012453 sprague-dawley rat model Methods 0.000 description 1
239000008117 stearic acid Substances 0.000 description 1
239000000021 stimulant Substances 0.000 description 1
230000000638 stimulation Effects 0.000 description 1
TYFQFVWCELRYAO-UHFFFAOYSA-L suberate(2-) Chemical compound [O-]C(=O)CCCCCCC([O-])=O TYFQFVWCELRYAO-UHFFFAOYSA-L 0.000 description 1
239000000126 substance Substances 0.000 description 1
125000001424 substituent group Chemical group 0.000 description 1
KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
LSNNMFCWUKXFEE-UHFFFAOYSA-L sulfite Chemical compound [O-]S([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-L 0.000 description 1
230000002889 sympathetic effect Effects 0.000 description 1
239000007916 tablet composition Substances 0.000 description 1
150000003892 tartrate salts Chemical class 0.000 description 1
238000003419 tautomerization reaction Methods 0.000 description 1
KKEYFWRCBNTPAC-UHFFFAOYSA-L terephthalate(2-) Chemical compound [O-]C(=O)C1=CC=C(C([O-])=O)C=C1 KKEYFWRCBNTPAC-UHFFFAOYSA-L 0.000 description 1
ISIJQEHRDSCQIU-UHFFFAOYSA-N tert-butyl 2,7-diazaspiro[4.5]decane-7-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CCCC11CNCC1 ISIJQEHRDSCQIU-UHFFFAOYSA-N 0.000 description 1
150000003556 thioamides Chemical class 0.000 description 1
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
125000003944 tolyl group Chemical group 0.000 description 1
238000002211 ultraviolet spectrum Methods 0.000 description 1
239000002351 wastewater Substances 0.000 description 1
229940071104 xylenesulfonate Drugs 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D513/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
- C07D513/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains two hetero rings
- C07D513/04—Ortho-condensed systems
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/02—Drugs for disorders of the urinary system of urine or of the urinary tract, e.g. urine acidifiers
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/20—Hypnotics; Sedatives
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/24—Antidepressants
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/26—Psychostimulants, e.g. nicotine, cocaine
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D215/20—Oxygen atoms
- C07D215/24—Oxygen atoms attached in position 8
- C07D215/26—Alcohols; Ethers thereof
- C07D215/30—Metal salts; Chelates
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings

Landscapes

Chemical & Material Sciences (AREA)
Health & Medical Sciences (AREA)
Organic Chemistry (AREA)
General Health & Medical Sciences (AREA)
Veterinary Medicine (AREA)
Public Health (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Bioinformatics & Cheminformatics (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
Engineering & Computer Science (AREA)
Biomedical Technology (AREA)
Neurosurgery (AREA)
Neurology (AREA)
Psychiatry (AREA)
Anesthesiology (AREA)
Heart & Thoracic Surgery (AREA)
Cardiology (AREA)
Pain & Pain Management (AREA)
Urology & Nephrology (AREA)
Endocrinology (AREA)
Reproductive Health (AREA)
Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Preparation Of Compounds By Using Micro-Organisms (AREA)

CN198585101547A 1984-04-27 1985-04-01 新型八氢噻唑[4，5-g]并喹啉化合物的制备方法及其用途 Pending CN85101547A (zh)

Priority Applications (1)

Application Number	Priority Date	Filing Date	Title
CN198585101547A CN85101547A (zh)	1984-04-27	1985-04-01	新型八氢噻唑[4，5-g]并喹啉化合物的制备方法及其用途

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
US06/604,687 US4537893A (en)	1984-04-27	1984-04-27	Octahydrothiazolo[4,5-g]quinolines and use as prolactin secretion inhibitors
CN198585101547A CN85101547A (zh)	1984-04-27	1985-04-01	新型八氢噻唑[4，5-g]并喹啉化合物的制备方法及其用途

Publications (1)

Publication Number	Publication Date
CN85101547A true CN85101547A (zh)	1987-01-24

Family

ID=24420601

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CN198585101547A Pending CN85101547A (zh)	1984-04-27	1985-04-01	新型八氢噻唑[4，5-g]并喹啉化合物的制备方法及其用途

Country Status (19)

Country	Link
US (1)	US4537893A (da)
EP (1)	EP0160502B1 (da)
JP (1)	JPH0631262B2 (da)
KR (1)	KR870001072B1 (da)
CN (1)	CN85101547A (da)
AT (1)	ATE67767T1 (da)
AU (1)	AU564946B2 (da)
CA (1)	CA1287356C (da)
DE (1)	DE3584183D1 (da)
DK (1)	DK185485A (da)
ES (1)	ES8704177A1 (da)
GR (1)	GR850989B (da)
HU (1)	HU193113B (da)
IL (1)	IL74988A0 (da)
NZ (1)	NZ211863A (da)
PH (1)	PH21951A (da)
PT (1)	PT80339B (da)
SU (1)	SU1414318A3 (da)
ZA (1)	ZA852999B (da)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
CN102088998A (zh) *	2008-05-14	2011-06-08	益普生制药股份有限公司	生长激素释放抑制因子-多巴胺缀合物的药物组合物

Families Citing this family (14)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US4778894A (en) *	1983-09-26	1988-10-18	Eli Lilly And Company	6 oxo-decahydroquinolines
US4977160A (en) *	1986-06-16	1990-12-11	Eli Lilly And Company	BCD tricyclic ergoline part-structure analogues
US5134143A (en) *	1986-06-16	1992-07-28	Eli Lilly And Company	BCD tricyclic ergoline part-structure analogues
US4826986A (en) *	1986-06-16	1989-05-02	Eli Lilly And Company	6-Oxo-trans-octa- and decahydroquinolines
DE3624607A1 (de) *	1986-07-21	1988-01-28	Boehringer Ingelheim Kg	Neue tetrahydrobenzothiazolo-chinoline ihre herstellung und verwendung
US4762843A (en) *	1986-09-15	1988-08-09	Warner-Lambert Company	Hetero [f] fused carbocyclic pyridines as dopaminergic agents
US4939259A (en) *	1989-07-24	1990-07-03	Eli Lilly And Company	2-oxo-pyrido[2,3-g]quinoline derivatives
US5006525A (en) *	1989-07-24	1991-04-09	Eli Lilly And Company	Dopamine agonists method
US4977149A (en) *	1989-07-24	1990-12-11	Eli Lilly And Company	Pyridoquinoline dopamine agonists, compositions and use
US5057515A (en) *	1989-07-24	1991-10-15	Eli Lilly And Company	Method for agonizing a dopamine receptor
US5416090A (en) *	1991-01-31	1995-05-16	Eli Lilly And Company	Method of treating inflammation
CA2144669A1 (en) *	1994-03-29	1995-09-30	Kozo Akasaka	Biphenyl derivatives
EP0816406B1 (de) *	1996-06-26	2000-09-06	Bayer Ag	Verfahren zur Herstellung salzarmer Präparationen von Kondensationsprodukten
TWI537274B (zh) *	2011-03-14	2016-06-11	橘生藥品工業股份有限公司	新穎之八氫噻吩并喹啉衍生物、含有其之醫藥組成物及該等之用途

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
DE2056224A1 (de) *	1969-11-17	1971-06-03	Danchi Seiyaku Co , Ltd , Tokio	Neue Thiazolochinohnderivate und Ver fahren zu ihrer Herstellung
US4198415A (en) *	1979-01-22	1980-04-15	Eli Lilly And Company	Prolactin inhibiting octahydro pyrazolo[3,4-g]quinolines
US4258049A (en) *	1979-07-02	1981-03-24	Smithkline Corporation	Inhibiting phenylethanolamine N-methyltransferase with thiadiazolo and oxadiazolotetrahydroisoquinolines
US4367231A (en) *	1979-09-14	1983-01-04	Eli Lilly And Company	Method of using octahydro pyrazolo[3,4-g]quinolines

1984
- 1984-04-27 US US06/604,687 patent/US4537893A/en not_active Expired - Fee Related
1985
- 1985-04-01 CN CN198585101547A patent/CN85101547A/zh active Pending
- 1985-04-22 CA CA000479702A patent/CA1287356C/en not_active Expired - Lifetime
- 1985-04-22 NZ NZ211863A patent/NZ211863A/en unknown
- 1985-04-22 ZA ZA852999A patent/ZA852999B/xx unknown
- 1985-04-22 SU SU853883101A patent/SU1414318A3/ru active
- 1985-04-23 IL IL74988A patent/IL74988A0/xx unknown
- 1985-04-23 GR GR850989A patent/GR850989B/el unknown
- 1985-04-23 PT PT80339A patent/PT80339B/pt not_active IP Right Cessation
- 1985-04-24 EP EP85302852A patent/EP0160502B1/en not_active Expired - Lifetime
- 1985-04-24 AU AU41666/85A patent/AU564946B2/en not_active Ceased
- 1985-04-24 DE DE8585302852T patent/DE3584183D1/de not_active Expired - Lifetime
- 1985-04-24 AT AT85302852T patent/ATE67767T1/de not_active IP Right Cessation
- 1985-04-25 PH PH32196A patent/PH21951A/en unknown
- 1985-04-25 KR KR1019850002803A patent/KR870001072B1/ko not_active Expired
- 1985-04-25 ES ES542565A patent/ES8704177A1/es not_active Expired
- 1985-04-25 DK DK185485A patent/DK185485A/da not_active Application Discontinuation
- 1985-04-26 HU HU851624A patent/HU193113B/hu unknown
- 1985-04-26 JP JP60092157A patent/JPH0631262B2/ja not_active Expired - Lifetime

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
CN102088998A (zh) *	2008-05-14	2011-06-08	益普生制药股份有限公司	生长激素释放抑制因子-多巴胺缀合物的药物组合物

Also Published As

Publication number	Publication date
EP0160502A2 (en)	1985-11-06
HU193113B (en)	1987-08-28
DK185485D0 (da)	1985-04-25
CA1287356C (en)	1991-08-06
JPH0631262B2 (ja)	1994-04-27
PT80339A (en)	1985-05-01
EP0160502B1 (en)	1991-09-25
ZA852999B (en)	1986-11-26
AU4166685A (en)	1985-10-31
JPS60233091A (ja)	1985-11-19
PH21951A (en)	1988-04-15
ES542565A0 (es)	1987-03-16
NZ211863A (en)	1987-10-30
IL74988A0 (en)	1985-08-30
HUT37624A (en)	1986-01-23
GR850989B (da)	1985-11-25
SU1414318A3 (ru)	1988-07-30
ES8704177A1 (es)	1987-03-16
PT80339B (en)	1987-02-16
DK185485A (da)	1985-10-28
AU564946B2 (en)	1987-09-03
EP0160502A3 (en)	1987-03-11
DE3584183D1 (de)	1991-10-31
KR870001072B1 (ko)	1987-05-27
KR850007261A (ko)	1985-12-02
ATE67767T1 (de)	1991-10-15
US4537893A (en)	1985-08-27

Legal Events

Date	Code	Title
1987-01-24	C06	Publication
1987-01-24	PB01	Publication
1988-10-12	WD01	Invention patent application deemed withdrawn after publication

Publication	Publication Date	Title
CN1028104C (zh)	1995-04-05	制备喹诺酮衍生物的方法
CN1094490C (zh)	2002-11-20	作为血清素拮抗剂的喹诺－2(1h)－酮衍生物
CN85101547A (zh)	1987-01-24	新型八氢噻唑[4，5-g]并喹啉化合物的制备方法及其用途
CN1049336C (zh)	2000-02-16	异恶唑衍生物在制备治疗肠应激综合征的组合物中的用途
CN1287487A (zh)	2001-03-14	氨基苯氧基乙酸衍生物和含有它们的药用组合物
CN86107754A (zh)	1987-08-05	噻唑并[4，5—c]喹啉
CN1384102A (zh)	2002-12-11	芳烷醇哌嗪衍生物及其在制备抗抑郁症药物中的应用
CN1191248C (zh)	2005-03-02	作为多巴胺d 受体亚型配体的1－(2－萘基)和1－(2－氮杂萘基)－4－(1－苯基甲基)哌嗪
CN1678614A (zh)	2005-10-05	N－甲基－N(3－{3－[2－噻吩基羰基]－吡唑－[1,5－α]－嘧啶－7－基}苯基)乙酰胺的新型多形体及其相关组合物和方法
CN1050604C (zh)	2000-03-22	具有抗精神病作用的化合物
CN1109870A (zh)	1995-10-11	N-(3-氨基丙基)-n-苯基-5，6，7，8-四氢化萘-2-羧酰胺衍生物衍生物、制法及应用
CN1016246B (zh)	1992-04-15	氨基酚衍生物的制备方法
CN1105358A (zh)	1995-07-19	N-取代氨杂双环庚烷衍生物，其制备方法以及用途
CN1798744A (zh)	2006-07-05	作为nmda/nr2b拮抗剂的3－氟－哌啶化合物
CN1023219C (zh)	1993-12-22	取代的咪唑衍生物的制备方法
CN1069491A (zh)	1993-03-03	2-(哌啶-1-基)乙醇衍生物，其制法及其治疗应用
CN1017901B (zh)	1992-08-19	抗精神病药稠环吡啶基哌嗪衍生物的制备方法
CN87100686A (zh)	1987-10-14	用作心血管剂的3-烷氧基-2-氨基丙胺类化合物
CN1134149A (zh)	1996-10-23	苯基吲哚化合物
CN1117729A (zh)	1996-02-28	吗啉衍生物
CN1050380A (zh)	1991-04-03	新的取代烷基哌啶及其作为胆固醇合成抑制剂的应用
CN1121403C (zh)	2003-09-17	喹喔啉二酮
CN1675194A (zh)	2005-09-28	新的芳基－{4－卤素－4－[(杂芳基甲氨基)甲基]－哌啶－1－基}甲酮衍生物、制备方法及其作为药物的用途
CN1027066C (zh)	1994-12-21	吲哚衍生物的制备方法
CN1036762A (zh)	1989-11-01	吡啶并嘧啶衍生物，含该衍生物的药物组合物及其制法

CN85101547A - 新型八氢噻唑[4，5-g]并喹啉化合物的制备方法及其用途 - Google Patents

Info

Links

Classifications

Landscapes

Priority Applications (1)

Applications Claiming Priority (2)

Publications (1)

Family

ID=24420601

Family Applications (1)

Country Status (19)

Cited By (1)

Families Citing this family (14)

Family Cites Families (4)

Cited By (1)

Also Published As

Similar Documents

Legal Events